Systems and methods for detecting fault conditions in electroporation therapy

ABSTRACT

Example systems, apparatuses, methods, and computer program products are disclosed for electroporating cells in a tissue using a set of voltage pulses generated by capacitor charge circuitry based on a voltage supply. An example method includes continuously monitoring a set of characteristics of the voltage supply and the set of voltage pulses; generating a first set of monitor signals based on the set of characteristics; detecting a first fault condition based on the first set of monitor signals; and generating a first crowbar trigger activation signal. The example computer method further includes: detecting a second fault condition based on a second set of monitor signals generated based on the first set of monitor signals; and generating a second crowbar trigger activation signal. Subsequently, the example computer method includes electrically disconnecting the capacitor charge circuitry from electroporation electrode circuitry based on either the first or second crowbar trigger activation signal.

TECHNOLOGICAL FIELD

Example embodiments of the present disclosure relate generally to theuse of control systems to improve an electroporation process and toincrease the permeability of cells, and more specifically to theoptimized application of controlled electric fields for delivery oftherapeutic moieties into cells by electroporation therapy (EPT), alsoknown as cell poration therapy (CPT) and electrochemotherapy (ECT).

BACKGROUND

In the 1970's scientists discovered that electric fields could be usedto create pores in cells without causing permanent damage. Thisdiscovery made possible the insertion of large molecules into cellcytoplasm. As a result, therapeutic moieties such as pharmacologicalcompounds now can be incorporated into live cells through a processknown as electroporation. The genes or other molecules are injected intothe live cells in and short pulses of high electric fields are applied.The cell membranes are transiently made porous and the genes ormolecules enter the cells, where they can modify the genome of the cell.

In the treatment of certain types of cancer with chemotherapy, it isnecessary to use a high enough dose of a drug to kill the cancer cellswithout killing an unacceptably high number of normal cells. If thechemotherapy drug could be inserted directly inside the cancer cells,this objective could be achieved. Some of the anti-cancer drugs, forexample, bleomycin, normally cannot penetrate the membranes of certaincancer cells effectively. However, electroporation makes it possible toinsert bleomycin into cells.

Treatment typically is carried out by injecting an anticancer drugdirectly into the tumor and applying an electric field to the tumorbetween a pair of electrodes. The field strength must be adjustedreasonably accurately so that electroporation of the cells of the tumoroccurs without damage, or at least minimal damage, to any normal orhealthy cells. This can normally be easily carried out with externaltumors by applying the electrodes to opposite sides of the tumor so thatthe electric field is between the electrodes. When the field is uniform,the distance between the electrodes can then be measured and a suitablevoltage according to the formula E=V/d can then be applied to theelectrodes (E=electric field strength in V/cm; V=voltage in volts; andd=distance in cm). When large or internal tumors are to be treated, itis not easy to properly locate electrodes and measure the distancebetween them.

Treatment of a subject using cell poration therapy provides a means foravoiding the deleterious effects typically associated withadministration of anticancer or cytotoxic agents. Such treatment wouldallow introduction of these agents to selectively damage or killundesirable cells while avoiding surrounding healthy cells or tissue.One issue, however, with using electroporation techniques is thatdiseased tissue, particularly cancerous tissue, can be quiteheterogeneous, requiring adjustment of electroporation conditions.

Applicant has identified a number of deficiencies and problemsassociated with conventional EPT techniques and electroporation systems,and safety features associated therewith. Through applied effort,ingenuity, and innovation, many of these identified problems have beensolved by developing solutions that are included in embodiments of thepresent disclosure, many examples of which are described in detailherein.

SUMMARY

Systems, apparatuses, methods, and computer program products aredisclosed herein for electroporating cells in a tissue using a set ofcontinuously monitored voltage pulses generated based on a continuouslymonitored voltage supply. Although the disclosure herein pertains to anyvoltage ranges, example embodiments will be described with reference tohigh voltage (HV) and low voltage (LV) ranges.

In one example embodiment, a system is provided for electroporatingcells in a tissue using a set of voltage pulses generated based on avoltage supply. The system may comprise voltage generation circuitry inelectrical communication with capacitor charge circuitry and monitorcircuitry. The voltage generation circuitry may be configured togenerate the voltage supply and transmit the voltage supply to thecapacitor charge circuitry. The system may further comprise thecapacitor charge circuitry. The capacitor charge circuitry may be inelectrical communication with the voltage generation circuitry, crowbartrigger circuitry, the monitor circuitry, and electroporation electrode(EPE) circuitry. The capacitor charge circuitry may be configured toreceive the voltage supply from the voltage generation circuitry,generate the set of voltage pulses based on the voltage supply, andtransmit the set of voltage pulses to the electroporation electrodecircuitry. The system may further comprise the monitor circuitry. Themonitor circuitry may be in electrical communication with the voltagegeneration circuitry, the capacitor charge circuitry, monitor analysiscircuitry, and the crowbar trigger circuitry. The monitor circuitry maybe configured to continuously monitor a set of characteristics of thevoltage supply and the set of voltage pulses, generate a first set ofmonitor signals based on the set of characteristics, and transmit thefirst set of monitor signals. The monitor circuitry may be furtherconfigured to: detect a first fault condition based on the first set ofmonitor signals; in response to detection of the first fault condition,generate a first crowbar trigger activation signal; and transmit thefirst crowbar trigger activation signal to the crowbar triggercircuitry. The system may further comprise the monitor analysiscircuitry. The monitor analysis circuitry may be in electricalcommunication with the crowbar trigger circuitry. The monitor analysiscircuitry may be configured to: receive a second set of monitor signalsgenerated based on the first set of monitor signals; detect a secondfault condition based on the second set of monitor signals; in responseto detection of the second fault condition, generate a second crowbartrigger activation signal; and transmit the second crowbar triggeractivation signal to the crowbar trigger circuitry. The system mayfurther comprise the crowbar trigger circuitry. The crowbar triggercircuitry may be in electrical communication with the monitor circuitryand the monitor analysis circuitry. The crowbar trigger circuitry may beconfigured to: receive the first crowbar trigger activation signal fromthe monitor circuitry; receive the second crowbar trigger activationsignal from the monitor analysis circuitry; and, in response to eitherreceipt of the first crowbar trigger activation signal or receipt of thesecond crowbar trigger activation signal, electrically disconnect thecapacitor charge circuitry from the electroporation electrode circuitry.

In another example embodiment, an apparatus is provided forelectroporating cells in a tissue using a set of voltage pulsesgenerated based on a voltage supply. The apparatus may comprise voltagegeneration circuitry in electrical communication with capacitor chargecircuitry and monitor circuitry. The voltage generation circuitry may beconfigured to generate the voltage supply and transmit the voltagesupply to the capacitor charge circuitry. The apparatus may furthercomprise the capacitor charge circuitry. The capacitor charge circuitrymay be in electrical communication with the voltage generationcircuitry, crowbar trigger circuitry, the monitor circuitry, andelectroporation electrode circuitry. The capacitor charge circuitry maybe configured to receive the voltage supply from the voltage generationcircuitry, generate the set of voltage pulses based on the voltagesupply, and transmit the set of voltage pulses to the electroporationelectrode circuitry. The apparatus may further comprise the monitorcircuitry. The monitor circuitry may be in electrical communication withthe voltage generation circuitry, the capacitor charge circuitry,monitor analysis circuitry, and the crowbar trigger circuitry. Themonitor circuitry may be configured to continuously monitor a set ofcharacteristics of the voltage supply and the set of voltage pulses,generate a first set of monitor signals based on the set ofcharacteristics, and transmit the first set of monitor signals. Themonitor circuitry may be further configured to: detect a first faultcondition based on the first set of monitor signals; in response todetection of the first fault condition, generate a first crowbar triggeractivation signal; and transmit the first crowbar trigger activationsignal to the crowbar trigger circuitry. The apparatus may furthercomprise the monitor analysis circuitry. The monitor analysis circuitrymay be in electrical communication with the crowbar trigger circuitry.The monitor analysis circuitry may be configured to: receive a secondset of monitor signals generated based on the first set of monitorsignals; detect a second fault condition based on the second set ofmonitor signals; in response to detection of the second fault condition,generate a second crowbar trigger activation signal; and transmit thesecond crowbar trigger activation signal to the crowbar triggercircuitry. The apparatus may further comprise the crowbar triggercircuitry. The crowbar trigger circuitry may be in electricalcommunication with the monitor circuitry and the monitor analysiscircuitry. The crowbar trigger circuitry may be configured to: receivethe first crowbar trigger activation signal from the monitor circuitry;receive the second crowbar trigger activation signal from the monitoranalysis circuitry; and, in response to either receipt of the firstcrowbar trigger activation signal or receipt of the second crowbartrigger activation signal, electrically disconnect the capacitor chargecircuitry from the electroporation electrode circuitry.

In another example embodiment, an apparatus is provided forelectroporating cells in a tissue using a set of voltage pulsesgenerated based on a voltage supply. The apparatus may comprise monitorcircuitry in electrical communication with crowbar trigger circuitry.The monitor circuitry may be configured to continuously monitor a set ofcharacteristics of the voltage supply and the set of voltage pulses. Themonitor circuitry may be further configured to generate a first set ofmonitor signals based on the set of characteristics. The monitorcircuitry may be further configured to transmit the first set of monitorsignals. The monitor circuitry may be further configured to detect afirst fault condition based on the first set of monitor signals. Themonitor circuitry may be further configured to, in response to detectionof the first fault condition, generate a first crowbar triggeractivation signal. The monitor circuitry may be further configured totransmit the first crowbar trigger activation signal to the crowbartrigger circuitry. The apparatus may further comprise monitor analysiscircuitry in electrical communication with the crowbar triggercircuitry. The monitor analysis circuitry may be configured to receive asecond set of monitor signals generated based on the first set ofmonitor signals. The monitor analysis circuitry may be furtherconfigured to detect a second fault condition based on the second set ofmonitor signals. The monitor analysis circuitry may be furtherconfigured to, in response to detection of the second fault condition,generate a second crowbar trigger activation signal. The monitoranalysis circuitry may be further configured to transmit the secondcrowbar trigger activation signal to the crowbar trigger circuitry. Theapparatus may further comprise the crowbar trigger circuitry. Thecrowbar trigger circuitry may be in electrical communication with themonitor circuitry and the monitor analysis circuitry. The crowbartrigger circuitry may be configured to receive the first crowbar triggeractivation signal from the monitor circuitry. The crowbar triggercircuitry may be further configured to receive the second crowbartrigger activation signal from the monitor analysis circuitry. Thecrowbar trigger circuitry may be further configured to, in response toeither receipt of the first crowbar trigger activation signal or receiptof the second crowbar trigger activation signal, electrically disconnectthe voltage supply from electroporation electrode circuitry.

In another example embodiment, a method is provided for electroporatingcells in a tissue using a set of voltage pulses generated based on avoltage supply. The method may comprise: generating, by voltagegeneration circuitry, the voltage supply; and transmitting, by thevoltage generation circuitry, the voltage supply to capacitor chargecircuitry. The method may further comprise: receiving, by the capacitorcharge circuitry, the voltage supply from the voltage generationcircuitry; generating, by the capacitor charge circuitry, the set ofvoltage pulses based on the voltage supply; and transmitting, by thecapacitor charge circuitry, the set of voltage pulses to electroporationelectrode circuitry. The method may further comprise: continuouslymonitoring, by monitor circuitry, a set of characteristics of thevoltage supply and the set of voltage pulses; generating, by the monitorcircuitry, a first set of monitor signals based on the set ofcharacteristics; transmitting, by the monitor circuitry, the first setof monitor signals; detecting, by the monitor circuitry, a first faultcondition based on the first set of monitor signals; in response todetecting the first fault condition, generating, by the monitorcircuitry, a first crowbar trigger activation signal; and transmitting,by the monitor circuitry, the first crowbar trigger activation signal tocrowbar trigger circuitry. The method may further comprise: receiving,by monitor analysis circuitry, a second set of monitor signals generatedbased on the first set of monitor signals; detecting, by the monitoranalysis circuitry, a second fault condition based on the second set ofmonitor signals; in response to detecting the second fault condition,generating, by the monitor analysis circuitry, a second crowbar triggeractivation signal; and transmitting, by the monitor analysis circuitry,the second crowbar trigger activation signal to the crowbar triggercircuitry. The method may further comprise: receiving, by the crowbartrigger circuitry, either the first crowbar trigger activation signal orthe second crowbar trigger activation signal; and in response to eitherreceiving the first crowbar trigger activation signal or receiving thesecond crowbar trigger activation signal, electrically disconnecting, bythe crowbar trigger circuitry, the capacitor charge circuitry from theelectroporation electrode circuitry.

In yet another example embodiment, a computer program product isprovided for electroporating cells in a tissue using a set of voltagepulses generated based on a voltage supply. The computer program productmay comprise at least one non-transitory computer-readable storagemedium storing computer-executable program code instructions that, whenexecuted by a computing system, cause the computing system to: generate,by voltage generation circuitry, the voltage supply; and transmit, bythe voltage generation circuitry, the voltage supply to capacitor chargecircuitry. The computer-executable program code instructions, whenexecuted by the computing system, may further cause the computing systemto: receive, by the capacitor charge circuitry, the voltage supply fromthe voltage generation circuitry; generate, by the capacitor chargecircuitry, the set of voltage pulses based on the voltage supply; andtransmit, by the capacitor charge circuitry, the set of voltage pulsesto electroporation electrode circuitry. The computer-executable programcode instructions, when executed by the computing system, may furthercause the computing system to receive, by monitor analysis circuitry, asecond set of monitor signals generated based on a first set of monitorsignals. The first set of monitor signals may have been generated, bymonitor circuitry, based on a continuously monitored set ofcharacteristics of the voltage supply and the set of voltage pulses. Thecomputer-executable program code instructions, when executed by thecomputing system, may further cause the computing system to: detect, bythe monitor analysis circuitry, a fault condition based on the secondset of monitor signals; in response to detecting the fault condition,generate, by the monitor analysis circuitry, a crowbar triggeractivation signal; and transmit, by the monitor analysis circuitry, thecrowbar trigger activation signal to the crowbar trigger circuitry. Thecomputer-executable program code instructions, when executed by thecomputing system, may further cause the computing system to: receive, bythe crowbar trigger circuitry, either the first crowbar triggeractivation signal or the second crowbar trigger activation signal; andin response to either receiving the first crowbar trigger activationsignal or receiving the second crowbar trigger activation signal,electrically disconnecting, by the crowbar trigger circuitry, thecapacitor charge circuitry from the electroporation electrode circuitry.

The above summary is provided merely for purposes of summarizing someexample embodiments to provide a basic understanding of some aspects ofthe disclosure. Accordingly, it will be appreciated that theabove-described embodiments are merely examples and should not beconstrued to narrow the scope or spirit of the disclosure in any way. Itwill be appreciated that the scope of the disclosure encompasses manypotential embodiments in addition to those here summarized, some ofwhich will be further described below.

BRIEF DESCRIPTION OF THE DRAWINGS

Having described certain example embodiments of the present disclosurein general terms above, reference will now be made to the accompanyingdrawings, which illustrate example embodiments and features of thepresent disclosure and are not necessarily drawn to scale. It will beunderstood that the components and structures illustrated in thedrawings may or may not be present in various embodiments of thedisclosure described herein. Accordingly, some embodiments or featuresof the present disclosure may include fewer or more components orstructures than those shown in the drawings while not departing from thescope of the disclosure.

FIG. 1 illustrates an example EPT treatment instrument in accordancewith some example embodiments described herein.

FIG. 2 illustrates an example schematic block diagram in accordance withsome example embodiments described herein.

FIG. 3A, FIG. 3B, FIG. 3C, and FIG. 3D illustrate example block diagramsfor an EPT treatment instrument in accordance with some exampleembodiments described herein.

FIG. 4A, FIG. 4B, and FIG. 4C illustrate example circuitry blockdiagrams in accordance with some example embodiments described herein.

FIG. 5A, FIG. 5B, FIG. 5C, FIG. 5D, FIG. 5E, FIG. 5F, FIG. 5G, FIG. 5H,FIG. 5I, and FIG. 5J illustrate example schematic diagrams in accordancewith some example embodiments described herein.

FIG. 6A, FIG. 6B, and FIG. 6C illustrate example pulse voltage signalsin accordance with some example embodiments described herein.

FIG. 7 illustrates an example flowchart illustrating an example methodin accordance with some example embodiments described herein.

DETAILED DESCRIPTION

The following description should be read with reference to the drawingswherein like reference numerals indicate like elements throughout theseveral views. The detailed description and drawings show severalembodiments which are meant to be illustrative of the disclosure. Itshould be understood that any numbering of disclosed features (e.g.,first, second, etc.) and/or directional terms used in conjunction withdisclosed features (e.g., front, back, under, above, etc.) are relativeterms indicating illustrative relationships between the pertinentfeatures.

It should be understood at the outset that although illustrativeimplementations of one or more aspects are illustrated below, thedisclosed assemblies, systems, and methods may be implemented using anynumber of techniques, whether currently known or not yet in existence.The disclosure should in no way be limited to the illustrativeimplementations, drawings, and techniques illustrated below, but may bemodified within the scope of the appended claims along with their fullscope of equivalents. While values for dimensions of various elementsare disclosed, the drawings may not be to scale.

The word “example,” when used herein, is intended to mean “serving as anexample, instance, or illustration.” Any implementation described hereinas an “example” is not necessarily preferred or advantageous over otherimplementations.

Example embodiments described herein provide systems, apparatuses,methods, and computer program products for an EPT treatment instrumentwhich provides for electroporating cells in a tissue using a set ofpulses (e.g., HV pulses, LV pulses) generated based on a voltage supply(e.g., an HV supply, an LV supply). In some instances, the EPT treatmentinstrument may provide redundant safety protocols comprisinghardware-based safety protocols (e.g., monitor circuitry 240) andsoftware-based safety protocols (e.g., executed by monitor analysiscircuitry 270). For example, the EPT treatment instrument disclosedherein provides for detecting fault conditions using four hardwaremonitoring circuitries in addition to four software monitoringcircuitries, each of which is configured to activate the crowbar triggercircuitry described herein in the event of a fault condition (e.g.,overvoltage, overcurrent). Further, if the crowbar trigger circuitryfails, the relay circuitry described herein comprises two relaysconfigured to cut off power and prevent dissipation of the overvoltageor overcurrent to the patient.

In some embodiments, the EPT treatment instrument disclosed hereinprovides for: continuously monitoring a set of characteristics of thevoltage supply and the set of voltage pulses; generating a set of analogmonitor signals based on the set of characteristics; detecting a firstfault condition (e.g., overvoltage, overcurrent) based on the analog setof monitor signals; detecting a second fault condition based on a set ofdigital monitor signals; and in response to either the detection of thefirst fault condition or the second fault condition, electricallydisconnecting, by crowbar trigger circuitry, the voltage pulses and thevoltage supply from the electroporation electrode needles to prevent theovervoltages and overcurrents from being applied to the patient.

In some embodiments, the EPT treatment instrument disclosed hereinprovides for using a lower voltage (e.g., 5 volts instead of 50 volts)during needle placement verification to provide improved safety for thepatient while verifying that the EPE needle electrode is properly inplace. For example, the EPT treatment instrument may be used with a lowvoltage electroporation assembly to provide for the detection of propertissue resistance and applicator resistance. In some embodiments, thevoltage used for low voltage applications is about 5 Vdc, In someembodiments, the voltages used for high voltage applications are betweenabout 400 Vdc and about 1300 Vdc.

There are many advantages of the embodiments disclosed herein, such as:improved detection of a fault condition by multiple, redundant analogand digital circuitries; preventing, by crowbar trigger circuitry, anyovervoltages or overcurrents from being applied to a patient; improvedpatient safety by using lower voltage pulses during needle placementverification; and increasing the speed of charging the capacitor chargecircuitry because the impedance monitor circuitry, rather than thecapacitor charge circuitry, is used for needle placement verification.

FIG. 1 is a diagram of an EPT treatment instrument 100 forelectroporating cells in a tissue using a set of pulses (e.g., HVpulses, LV pulses) generated based on a voltage supply. Anelectroporation electrode applicator 112 may be removably coupled to theEPT treatment instrument 100, which may be configured to selectivelyapply voltage pulses to selected electroporation electrode needles 114of the electroporation electrode applicator 112. The pulse duration,voltage level, and electroporation electrode needle addressing orswitching pattern output by the EPT treatment instrument 100 are allprogrammable.

A display 116 indicates the therapy voltage setpoint. A remote therapyactivation connection 118 is provided to accommodate a foot pedal switch120 for activating pulses to the electroporation electrode applicator112. The foot pedal switch 120 permits a physician to activate the EPTtreatment instrument 100 while freeing both hands for positioning of theelectroporation electrode applicator 112 in a patient's tissue. Statusindicator lights 122 for power on (122A), fault detection (122B), andcompletion of a therapy session (122C) are provided for convenience.Electroporation electrode indicator lights 124 are provided topositively indicate that an electroporation electrode applicator 112 isconnected to the EPT treatment instrument 100 and to indicate the typeof electroporation electrode needle array (e.g., 4, 6, 9, or 16electroporation electrode needles). A standby/reset button 126 isprovided to “pause” the instrument and reset all functions of the EPTtreatment instrument 100 to a default state. A ready button 128 isprovided to prepare the EPT treatment instrument 100 for a therapysession. A prominent “therapy in process” indicator light 130 indicatesthat voltage pulses are being applied to the electroporation electrodeneedles 114. In addition, the EPT treatment instrument 100 may haveaudio indicators for such functions as a button press, a fault state,commencement or termination of a therapy session, indication of therapyin process, and other suitable functions.

In some embodiments, the EPT treatment instrument 100 may provide forelectroporating cells in a tissue using a set of voltage pulsesgenerated based on a voltage supply. The EPT treatment instrument 100may provide for generating the voltage supply, generating the set ofvoltage pulses based on the voltage supply, and transmitting the set ofvoltage pulses to the electroporation electrode needles 114. The EPTtreatment instrument 100 may further provide for: continuouslymonitoring a set of characteristics of the voltage supply and the set ofvoltage pulses; generating a set of analog monitor signals based on theset of characteristics; detecting a first fault condition (e.g.,overvoltage, overcurrent) based on the analog set of monitor signals;detecting a second fault condition (e.g., overvoltage, overcurrent)based on a set of digital monitor signals (e.g., digitized versions ofthe analog set of monitor signals); and in response to either thedetection of the first fault condition or the second fault condition,electrically disconnecting, by crowbar trigger circuitry disposed in theEPT treatment instrument 100, the voltage pulses and the voltage supplyfrom the electroporation electrode needles 114 to prevent theovervoltages and overcurrents from being applied to the patient.

In some embodiments, the EPT treatment instrument 100 may be coupled toa feedback sensor configured to detect the patient's heart beats. Bysynchronizing the application of voltage pulses near the heart to safeperiods between heart beats, the possibility of the applied voltagepulses interfering with normal heart rhythms may be reduced. Additionaldisclosure relating to EPT treatment instruments and the advantagesthereof are disclosed in U.S. Pat. No. 7,412,284, issued Aug. 12, 2008,and U.S. patent application Ser. No. 15/563,462, filed Sep. 29, 2017,both of which are herein incorporated by reference in their entireties.

The EPT treatment instrument 100 described with reference to FIG. 1 maybe embodied by one or more apparatuses, such as apparatus 200 shown inFIG. 2. The apparatus 200 may be configured to execute the operationsdescribed above with respect to FIG. 1 and below with respect to FIG.3A, FIG. 3B, FIG. 3C, FIG. 3D, FIG. 4A, FIG. 4B, FIG. 4C, FIG. 5A, FIG.5B, FIG. 5C, FIG. 5D, FIG. 5E, FIG. 5F, FIG. 5G, FIG. 5H, FIG. 5I, FIG.5J, FIG. 6A, FIG. 6B, FIG. 6C and FIG. 7. Although some of thesecomponents 210-296 are described with respect to their functionalcapabilities, it should be understood that the particularimplementations necessarily include the use of particular hardware toimplement such functional capabilities. It should also be understoodthat certain of these components 210-296 may include similar or commonhardware. For example, two sets of circuitry may both leverage use ofthe same electrical connection, ADC, network interface, processor,memory, or the like to perform their associated functions, such thatduplicate hardware is not required for each set of circuitry.

The use of the term “circuitry” as used herein with respect tocomponents of the apparatus 200 therefore includes particular hardwareconfigured to perform the functions associated with respective circuitrydescribed herein. Of course, while the term “circuitry” should beunderstood broadly to include hardware, in some embodiments, circuitrymay also include program code instructions for configuring the hardware.For example, in some embodiments, “circuitry” may include processingcircuitry (e.g., digital signal processing (DSP) components), storagemedia, network interfaces, input-output devices, and other components.In some embodiments, other elements of the apparatus 200 may provide orsupplement the functionality of particular circuitry. For example, theprocessor 262 may provide processing functionality, memory 264 mayprovide storage functionality, and communications circuitry 268 mayprovide network interface functionality, among other features.

As illustrated in FIG. 2, the apparatus 200 may include HV circuitry210, electroporation electrode (EPE) circuitry 220, crowbar triggercircuitry 230, monitor circuitry 240 (e.g., hardware-based monitorcircuitry), processing circuitry 260, control circuitry 290, andanalog-to-digital conversion (ADC) circuitry 296. The HV circuitry 210may include HV generation circuitry 212, gate drive circuitry 214, andcapacitor charge circuitry 216. The EPE circuitry 220 may include HVrelay circuitry 222 (e.g., comprising a set of relays) and EPE needlecircuitry 224. The monitor circuitry 240 may include impedance monitorcircuitry 242, current monitor circuitry 244, pulse monitor circuitry246, capacity monitor circuitry 248, HV monitor circuitry 250, and HVsupply monitor circuitry 252. The processing circuitry 260 may includeprocessor 262, memory 264, input-output circuitry 266, communicationscircuitry 268, user interface circuitry 269, and monitor analysiscircuitry 270 (e.g., software-based monitor circuitry). The monitoranalysis circuitry 270 may include impedance monitor analysis circuitry272, current monitor analysis circuitry 274, pulse monitor analysiscircuitry 276, capacity monitor analysis circuitry 278, HV monitoranalysis circuitry 280, and crowbar trigger control signal generationcircuitry 282. The control circuitry 290 may include digitalpotentiometer (pot) circuitry 292 and digital pot HV control circuitry294.

The HV generation circuitry 212 may be in electrical communication withthe gate drive circuitry 214, the capacitor charge circuitry 216, themonitor circuitry 240, the processing circuitry 260, the digital pot HVcontrol circuitry 294, and the ADC circuitry 296. The HV generationcircuitry 212 may be configured to generate a voltage supply (e.g., anHV supply, an LV supply) and transmit the voltage supply to thecapacitor charge circuitry 216. The capacitor charge circuitry 216 maybe in electrical communication with the HV generation circuitry 212, thecrowbar trigger circuitry 230, the monitor circuitry 240, and the EPEcircuitry 220. The capacitor charge circuitry 216 may be configured toreceive the voltage supply from the HV generation circuitry 212,generate the set of voltage pulses (e.g., HV pulses, LV pulses) based onthe voltage supply, and transmit the set of voltage pulses to theelectroporation electrode circuitry 220 (e.g., via HV relay circuitry222). In some embodiments, a set of voltage pulses may include fromabout 6 to about 10 pulses per set. In some embodiments, the duration(e.g., pulse width) of each voltage pulse in the set of voltage pulsesmay be between about 70 microseconds and about 150 microseconds. In someembodiments, the duration (e.g., pulse width) of each voltage pulse inthe set of voltage pulses may be from about 100 microseconds to about 1millisecond. For example, the duration of each voltage pulse in the setof voltage pulses may be about 100 microseconds. In some embodiments,the term “voltage” refers to direct current (DC) voltage, and the term“volts” refers to Vdc. In some embodiments, the HV generation circuitry212 may be referred to as “voltage generation circuitry” and maycomprise HV generation circuitry configured to generate an HV supply, LVgeneration circuitry configured to generate an LV supply, or both. Inother embodiments, the LV generation circuitry may be comprised by theapparatus 200 apart from the HV generation circuitry. In someembodiments, the voltage of the HV supply may be between about 600 voltsand 3,000 volts, using a field strength of 700V/cm or greater. In someembodiments, the voltage of the HV supply may be between about 1,000volts and 1,750 volts, and the amperage of the HV supply may be betweenabout 40 amps and 60 amps. For example, the voltage of the HV supply maybe about 1,500 volts, and the amperage of the HV supply may be about 70amps. In some embodiments, the voltage of the HV supply may be betweenabout 400 volts and 1,300 volts. In some embodiments, the voltage of anLV supply generated by the HV generation circuitry 212 or by a separateLV generation circuitry comprised by the apparatus 200, may be about 5volts.

The monitor circuitry 240 may be in electrical communication with the HVgeneration circuitry 212, the capacitor charge circuitry 216, monitoranalysis circuitry 270, and the crowbar trigger circuitry 230. Themonitor circuitry 240 may be configured to continuously monitor a set ofcharacteristics of the voltage supply and the set of voltage pulses,generate a first set of monitor signals based on the set ofcharacteristics, and transmit the first set of monitor signals todigital pot circuitry 292, ADC circuitry 296. The first set of monitorsignals may include a set of analog monitor signals, such as an analogcontinuously monitored HV voltage signal (HV_MON), an analogcontinuously monitored capacitor voltage signal (CAP_MON, VAR_CAP_V), ananalog continuously monitored pulse voltage signal (PULSE_MON,VAR_PULSE_V), an analog continuously monitored current signal(CURRENT_MON), an analog continuously monitored impedance voltage signal(IMPEDANCE_MON), an analog continuously monitored HV supply voltagesignal (BV_MON), an analog continuously monitored HV supply currentsignal (BC_MON), any other suitable analog monitor signal, or anycombination thereof.

The monitor circuitry 240 may be further configured to: detect a firstfault condition based on the first set of monitor signals; in responseto detection of the first fault condition, generate a first crowbartrigger activation signal; and transmit the first crowbar triggeractivation signal to the crowbar trigger circuitry 230. The first faultcondition may comprise an analog fault condition, such as an analog HVovervoltage condition, an analog capacitor overvoltage condition, ananalog pulse overvoltage signal condition, an analog overcurrent signalcondition, any other suitable analog fault condition, or any combinationthereof. The first crowbar trigger activation signal may comprise ananalog crowbar trigger activation signal, such as an HV overvoltagesignal (nHV_OV), a capacitor overvoltage signal (nCAP_OV), a pulseovervoltage signal (nPULSE_OV), an overcurrent signal (nOVER_CURRENT),any other suitable analog crowbar trigger activation signal, or anycombination thereof.

In some embodiments, the monitor circuitry 240 may comprise HV monitorcircuitry 250. The HV monitor circuitry 250 may be configured to:continuously monitor an HV voltage (+HV) of the HV supply, wherein theset of characteristics comprises the continuously monitored HV voltage;generate a first continuously monitored HV voltage signal (HV_MON) basedon the continuously monitored HV voltage, wherein the first set ofmonitor signals comprises the first continuously monitored HV voltagesignal; detect a first HV overvoltage condition (e.g., an analog HVvoltage above or equal to 1,512 volts for an HV supply voltage of 1,500volts) based on the first continuously monitored HV voltage signal,wherein the first fault condition is the first HV overvoltage condition;and, in response to detection of the first HV overvoltage condition,generate a first HV overvoltage signal (nHV_OV), wherein the firstcrowbar trigger activation signal is the first HV overvoltage signal.

In some embodiments, the monitor circuitry 240 may comprise capacitymonitor circuitry 248. The capacity monitor circuitry 248 may beconfigured to: continuously monitor a capacitor voltage (CAP_V) of thecapacitor charge circuitry 216, wherein the set of characteristicscomprises the continuously monitored capacitor voltage; generate a firstcontinuously monitored capacitor voltage signal (CAP_MON) based on thecontinuously monitored capacitor voltage, wherein the first set ofmonitor signals comprises the first continuously monitored capacitorvoltage signal; detect a first capacitor overvoltage condition (e.g., ananalog capacitor voltage in excess of an analog capacitor voltageovervoltage (VAR_CAP_V)) based on the first continuously monitoredcapacitor voltage signal, wherein the first fault condition is the firstcapacitor overvoltage condition; and, in response to detection of thefirst capacitor overvoltage condition, generate a first capacitorovervoltage signal (nCAP_OV), wherein the first crowbar triggeractivation signal is the first capacitor overvoltage signal.

In some embodiments, the monitor circuitry 240 may comprise pulsemonitor circuitry 246. The pulse monitor circuitry 246 may be configuredto: continuously monitor a pulse voltage (−HV_PULSE) of the set of HVpulses, wherein the set of characteristics comprises the continuouslymonitored pulse voltage; generate a first continuously monitored pulsevoltage signal (PULSE_MON) based on the continuously monitored pulsevoltage, wherein the first set of monitor signals comprises the firstcontinuously monitored pulse voltage signal; detect a first pulseovervoltage condition (e.g., an analog pulse voltage in excess of ananalog pulse voltage overvoltage (VAR_PULSE_V)) based on the firstcontinuously monitored pulse voltage signal, wherein the first faultcondition is the first pulse overvoltage condition; and in response todetection of the first pulse overvoltage condition, generate a firstpulse overvoltage signal (nPULSE_OV), wherein the first crowbar triggeractivation signal is the first pulse overvoltage signal.

In some embodiments, the monitor circuitry 240 may comprise currentmonitor circuitry 244. The current monitor circuitry 244 may beconfigured to: continuously monitor a current of the set of HV pulses,wherein the set of characteristics comprises the continuously monitoredcurrent; generate a first continuously monitored current signal(CURRENT_MON) based on the continuously monitored current, wherein thefirst set of monitor signals comprises the first continuously monitoredcurrent signal; detect a first overcurrent condition (e.g., an analogcurrent in excess of an analog current overcurrent value) based on thefirst continuously monitored current signal, wherein the first faultcondition is the first overcurrent condition; and in response todetection of the first overcurrent condition, generate a firstovercurrent signal (nOVER_CURRENT), wherein the first crowbar triggeractivation signal is the first overcurrent signal.

In some embodiments, the monitor circuitry 240 may be in electricalcommunication with a set of relays comprised by the HV relay circuitry222. The monitor circuitry 240 may comprise impedance monitor circuitry242. The impedance monitor circuitry 242 may be configured to: generatea set of low voltage (LV) pulses (e.g., 5 volts instead of 50 volts);transmit the set of LV pulses to the electroporation electrode circuitry220; receive a set of LV return pulses from the electroporationelectrode circuitry 220; monitor a resistance of the tissue based on theset of LV return pulses; and generate a first monitored impedancevoltage signal (IMPEDANCE_MON) based on the monitored resistance. Theimpedance monitor circuitry 242 may be further configured to: detect afirst impedance testing fault condition (e.g., an analog resistance lessthan a typical skin resistance (e.g., 20 ohms)) based on the firstmonitored impedance voltage signal; and, in response to detection of thefirst impedance testing fault condition, generate a first set of relaydeactivation signals; and transmit the first set of relay deactivationsignals to the set of relays. Each relay in the set of relays may beconfigured to: receive one of the relay deactivation signals in thefirst set of relay deactivation signals from the impedance monitorcircuitry 242; and, in response to receipt of the one of the relaydeactivation signals in the first set of relay deactivation signals,electrically disconnect the capacitor charge circuitry 216 from the EPEneedle circuitry 224.

The monitor analysis circuitry 270 may be in electrical communicationwith the crowbar trigger circuitry 230 and the ADC circuitry 296. Themonitor analysis circuitry 270 may be configured to: receive a secondset of monitor signals generated based on the first set of monitorsignals; detect a second fault condition based on the second set ofmonitor signals; in response to detection of the second fault condition,generate a second crowbar trigger activation signal; and transmit thesecond crowbar trigger activation signal to the crowbar triggercircuitry. The second set of monitor signals may include a set ofdigital monitor signals, such as a digital continuously monitored HVvoltage signal (digital HV_MON), a digital continuously monitoredcapacitor voltage signal (digital CAP_MON, digital VAR_CAP_V), a digitalcontinuously monitored pulse voltage signal (digital PULSE_MON, digitalVAR_PULSE_V), a digital continuously monitored current signal (digitalCURRENT_MON), a digital continuously monitored impedance voltage signal(digital IMPEDANCE_MON), a digital continuously monitored HV supplyvoltage signal (digital BV_MON), a digital continuously monitored HVsupply current signal (digital BC_MON), any other suitable digitalmonitor signal, or any combination thereof. In some embodiments, themonitor analysis circuitry 270 may be configured to receive the secondset of monitor signals from the ADC circuitry 296. For example, thefirst set of monitor signals may be a set of analog monitor signalstransmitted by the monitor circuitry 240 to the ADC circuitry 296, andthe second set of monitor signals may be a set of digital monitorsignals generated by the ADC circuitry 296 based on the set of analogmonitor signals and transmitted by the ADC circuitry 296 to the monitoranalysis circuitry 270.

The monitor analysis circuitry 270 may be further configured to: detecta second fault condition based on the second set of monitor signals; inresponse to detection of the second fault condition, generate a secondcrowbar trigger activation signal; and transmit the second crowbartrigger activation signal to the crowbar trigger circuitry. The secondcrowbar trigger activation signal may comprise a digital crowbar triggeractivation signal (nMICRO_CROWBAR), any other suitable crowbar triggeractivation signal, or any combination thereof.

In some embodiments, the monitor analysis circuitry 270 may be inelectrical communication with a set of relays comprised by the HV relaycircuitry 222. The monitor analysis circuitry 270 may be furtherconfigured to: in response to the detection of the second faultcondition, generate a set of relay deactivation signals; and transmitthe set of relay deactivation signals to the set of relays. Each relayin the set of relays may be configured to: receive one of the relaydeactivation signals in the set of relay deactivation signals from themonitor analysis circuitry; and, in response to receipt of the one ofthe relay deactivation signals, electrically disconnect the capacitorcharge circuitry 216 from the EPE needle circuitry 224.

In some embodiments, the monitor analysis circuitry 270 may comprise HVmonitor analysis circuitry 280 and crowbar trigger control signalgeneration circuitry 282. The HV monitor analysis circuitry 280 may beconfigured to: receive a second continuously monitored HV voltage signal(digital HV_MON) generated based on the first continuously monitored HVvoltage signal, wherein the second set of monitor signals comprises thesecond continuously monitored HV voltage signal; detect a second HVovervoltage condition (e.g., a digital HV voltage above or equal to1,512 volts for an HV supply voltage of 1,500 volts) based on the secondcontinuously monitored HV voltage signal, wherein the second faultcondition is the second HV overvoltage condition; in response todetection of the second HV overvoltage condition, generate a second HVovervoltage signal; and transmit the second HV overvoltage signal to thecrowbar trigger control signal generation circuitry 282. The crowbartrigger control signal generation circuitry 282 may be configured toreceive the second HV overvoltage signal from the HV monitor analysiscircuitry 280; in response to receipt of the second HV overvoltagesignal, generate the second crowbar trigger activation signal(nMICRO_CROWBAR); and transmit the second crowbar trigger activationcontrol signal to the crowbar trigger circuitry 230.

In some embodiments, the monitor analysis circuitry 270 may comprisecapacity monitor analysis circuitry 278 and crowbar trigger controlsignal generation circuitry 282. The capacity monitor analysis circuitry278 may be configured to: receive a second continuously monitoredcapacitor voltage signal (digital CAP_MON) generated based on the firstcontinuously monitored capacitor voltage signal, wherein the second setof monitor signals comprises the second continuously monitored capacitorvoltage signal; detect a second capacitor overvoltage condition (e.g., adigital capacitor voltage in excess of a digital capacitor voltageovervoltage (digital VAR_CAP_V)) based on the second continuouslymonitored capacitor voltage signal, wherein the second fault conditionis the second capacitor overvoltage condition; in response to detectionof the second capacitor overvoltage condition, generate a secondcapacitor overvoltage signal; and transmit the second capacitorovervoltage signal to the crowbar trigger control signal generationcircuitry 282. The crowbar trigger control signal generation circuitry282 may be configured to: receive the second capacitor overvoltagesignal from the capacity monitor analysis circuitry 278; in response toreceipt of the second capacitor overvoltage signal, generate the secondcrowbar trigger activation signal (nMICRO_CROWBAR); and transmit thesecond crowbar trigger activation control signal to the crowbar triggercircuitry 230.

In some embodiments, the monitor analysis circuitry 270 may comprisepulse monitor analysis circuitry 276 and crowbar trigger control signalgeneration circuitry 282. The pulse monitor analysis circuitry 276 maybe configured to: receive a second continuously monitored pulse voltagesignal (digital PULSE_MON) generated based on the first continuouslymonitored pulse voltage signal, wherein the second set of monitorsignals comprises the second continuously monitored pulse voltagesignal; detect a second pulse overvoltage condition (e.g., a digitalpulse voltage in excess of a digital pulse voltage overvoltage (digitalVAR_PULSE_V)) based on the second continuously monitored pulse voltagesignal, wherein the second fault condition is the second pulseovervoltage condition; in response to detection of the second pulseovervoltage condition, generate a second pulse overvoltage signal; andtransmit the second pulse overvoltage signal to the crowbar triggercontrol signal generation circuitry 282. The crowbar trigger controlsignal generation circuitry 282 may be configured to receive the secondpulse overvoltage signal from the pulse monitor analysis circuitry 276;in response to receipt of the second pulse overvoltage signal, generatethe second crowbar trigger activation signal (nMICRO_CROWBAR); andtransmit the crowbar trigger activation control signal to the crowbartrigger circuitry 230.

In some embodiments, the pulse monitor analysis circuitry 276 may befurther configured to: determine a rise time of a rising edge of a pulsein the set of pulses; and detect the second pulse overvoltage condition(e.g., a rise time in excess of a predetermined rise time thresholdvalue) based on the rise time. In some embodiments, the pulse monitoranalysis circuitry 276 may be further configured to: determine a falltime of a falling edge of a pulse in the set of pulses; and detect thesecond pulse overvoltage condition (e.g., a fall time in excess of apredetermined fall time threshold value) based on the fall time.

In some embodiments, the monitor analysis circuitry 270 may comprisecurrent monitor analysis circuitry 274 and crowbar trigger controlsignal generation circuitry 282. The current monitor analysis circuitry274 may be configured to: receive a second continuously monitoredcurrent signal (digital CURRENT_MON) generated based on the firstcontinuously monitored current signal, wherein the second set of monitorsignals comprises the second continuously monitored current signal;detect a second overcurrent condition (e.g., a digital current in excessof a digital current overcurrent value) based on the second continuouslymonitored current signal, wherein the second fault condition is thesecond overcurrent condition; in response to detection of the secondovercurrent condition, generate a second overcurrent signal; andtransmit the second overcurrent signal to the crowbar trigger controlsignal generation circuitry 282. The crowbar trigger control signalgeneration circuitry 282 may be configured to: receive the secondovercurrent signal from the current monitor analysis circuitry 274; inresponse to receipt of the second overcurrent signal, generate thesecond crowbar trigger activation signal (nMICRO_CROWBAR); and transmitthe second crowbar trigger activation control signal to the crowbartrigger circuitry 230.

In some embodiments, the monitor analysis circuitry 270 may be inelectrical communication with the set of relays comprised by the HVrelay circuitry 222. The monitor analysis circuitry 270 may compriseimpedance monitor analysis circuitry 272. The impedance monitor analysiscircuitry 272 may be configured to: receive a second monitored impedancevoltage signal (digital IMPEDANCE_MON) generated based on the firstmonitored impedance voltage signal; detect a second impedance testingfault condition (e.g., a digital resistance less than 20 ohms) based onthe second monitored impedance voltage signal; in response to detectionof the second monitored impedance voltage signal, generate a second setof relay deactivation signals; and transmit the second set of relaydeactivation signals to the set of relays. Each relay in the set ofrelays may be configured to: receive one of the relay deactivationsignals in the second set of relay deactivation signals from theimpedance monitor analysis circuitry; and in response to receipt of theone of the relay deactivation signals in the second set of relaydeactivation signals, electrically disconnect the capacitor chargecircuitry 216 from the EPE needle circuitry 224.

The crowbar trigger circuitry 230 may be in electrical communicationwith the monitor circuitry 240 and the monitor analysis circuitry 270.The crowbar trigger circuitry 230 may be configured to: receive thefirst crowbar trigger activation signal from the monitor circuitry 240;receive the second crowbar trigger activation signal from the monitoranalysis circuitry 270; and, in response to either receipt of the firstcrowbar trigger activation signal or receipt of the second crowbartrigger activation signal, electrically disconnect the HV circuitry 210from the electroporation electrode circuitry 220, such as byelectrically disconnecting the capacitor charge circuitry 216 from theelectroporation electrode circuitry 220. In some embodiments, thecrowbar trigger circuitry 230 may be configured to electricallydisconnect the capacitor charge circuitry 216 from the electroporationelectrode circuitry 220 within about 10 microseconds of the detection ofthe first fault condition or the detection of the second faultcondition.

The processor 262 may be embodied in a number of different ways and may,for example, include one or more processing devices configured toperform independently. Additionally or alternatively, the processor 262may include one or more processors configured in tandem via a bus toenable independent execution of instructions, pipelining,multithreading, or a combination thereof. The term “processor” or“processing circuitry” may be understood to include a single coreprocessor, a multi-core processor, multiple processors internal to theapparatus 200, remote or “cloud” processors, or a combination thereof.

In an example embodiment, the processor 262 may be configured to executeinstructions stored in the memory 264 or otherwise accessible to theprocessor 262. Alternatively or additionally, the processor 262 may beconfigured to execute hard-coded functionality. As such, whetherconfigured by hardware or software methods, or by a combination ofhardware with software, the processor 262 may represent an entity (e.g.,physically embodied in circuitry) capable of performing operationsaccording to an embodiment of the present disclosure while configuredaccordingly. As another example, when the processor 262 is embodied asan executor of program code instructions, the instructions mayspecifically configure the processor to perform the operations describedherein when the instructions are executed.

In some embodiments, the processor 262 (and/or co-processor or any otherprocessing circuitry assisting or otherwise associated with theprocessor) may be in communication with the memory 264 via a bus forpassing information among components of the apparatus. The memory 264may be non-transitory and may include, for example, one or more volatileand/or non-volatile memories. For example, the memory 264 may be anelectronic storage device (e.g., a computer readable storage medium). Inanother example, the memory 264 may be a non-transitorycomputer-readable storage medium storing computer-executable programcode instructions that, when executed by a computing system, cause thecomputing system to perform the various operations described herein. Thememory 264 may be configured to store information, data, content,signals applications, instructions (e.g., computer-executable programcode instructions), or the like, for enabling the apparatus 200 to carryout various functions in accordance with example embodiments of thepresent disclosure. For example, the memory 264 may be configured tostore monitor signals, fault condition (e.g., overvoltage, overcurrent)detection techniques, crowbar trigger control signals (e.g., crowbartrigger activation signals), relay controls, control signals, or anycombination or combinations thereof. It will be understood that thememory 264 may be configured to store partially or wholly any electronicinformation, data, data structures, signals, embodiments, examples,figures, processes, operations, techniques, algorithms, instructions,systems, apparatuses, methods, or computer program products describedherein, or any combination thereof.

In some embodiments, the processing circuitry 260 may includeinput-output circuitry 266 that may, in turn, be in communication withprocessor 262 to provide output to the user and, in some embodiments, toreceive input such as a command provided by the user. The input-outputcircuitry 266 may comprise a user interface, such as a graphical userinterface (GUI), and may include a display that may include a web userinterface, a GUI application, a mobile application, a client device, orany other suitable hardware or software. In some embodiments, theinput-output circuitry 266 may also include a keyboard, a mouse, ajoystick, a display device, a display screen, a touch screen, touchareas, soft keys, a microphone, a speaker, or other input-outputmechanisms. The processor 262, input-output circuitry 266 (which mayutilize the processor 262), or both may be configured to control one ormore functions of one or more user interface elements throughcomputer-executable program code instructions (e.g., software, firmware)stored in a non-transitory computer-readable storage medium (e.g.,memory 264). Input-output circuitry 266 is optional and, in someembodiments, the apparatus 200 may not include input-output circuitry.For example, where the apparatus 200 does not interact directly with theuser, the apparatus 200 may generate user interface data for display byone or more other devices with which one or more users directly interactand transmit the generated user interface data to one or more of thosedevices. For example, the apparatus 200, using user interface circuitry269, may generate user interface data for display by one or more displaydevices and transmit the generated user interface data to those displaydevices.

The communications circuitry 268 may be any device or circuitry embodiedin either hardware or a combination of hardware and software that isconfigured to receive or transmit data from or to a network or any otherdevice, circuitry, or module in communication with the apparatus 200. Inthis regard, the communications circuitry 268 may include, for example,a network interface for enabling communications with a wired or wirelesscommunication network. For example, the communications circuitry 268 mayinclude one or more network interface cards, antennae, buses, switches,routers, modems, and supporting hardware and/or software, or any otherdevice suitable for enabling communications via a network. In someembodiments, the communication interface may include the circuitry forinteracting with the antenna(s) to cause transmission of signals via theantenna(s) or to handle receipt of signals received via the antenna(s).These signals may be transmitted or received by the apparatus 200 usingany of a number of Internet, Ethernet, cellular, satellite, or wirelesstechnologies, such as IEEE 802.11, Code Division Multiple Access (CDMA),Global System for Mobiles (GSM), Universal Mobile TelecommunicationsSystem (UMTS), Long-Term Evolution (LTE), Bluetooth® v1.0 through v5.0,Bluetooth Low Energy (BLE), infrared wireless (e.g., IrDA),ultra-wideband (UWB), induction wireless transmission, Wi-Fi, near fieldcommunications (NFC), Worldwide Interoperability for Microwave Access(WiMAX), radio frequency (RF), RFID, or any other suitable technologies.

In some embodiments, communications circuitry 268 may comprise hardwarecomponents designed or configured to receive, from a user device, anelectronic indication of a pulse duration (e.g., 100 microseconds),voltage level (e.g., 1,500 volts), and EPE needle addressing orswitching pattern output by the apparatus 200. In some embodiments, thecommunications circuitry 268 may receive the electronic indication inresponse to a user using input-output circuitry 266 to select a pulseduration, voltage level, or EPE needle addressing or switching patternfrom a list of pulse durations, voltage levels, or EPE needle addressingor switching patterns displayed in a graphical user interface providedby user interface circuitry 269.

The user interface circuitry 269 includes hardware components designedor configured to receive, process, generate, and transmit data, such asuser interface data. For instance, the user interface circuitry 269includes hardware components designed or configured to generate userinterface data based on any embodiment or combination of embodimentsdescribed with reference to FIG. 1, FIG. 2, FIG. 3A, FIG. 3B, FIG. 3C,FIG. 3D, FIG. 4A, FIG. 4B, FIG. 4C, FIG. 5A, FIG. 5B, FIG. 5C, FIG. 5D,FIG. 5E, FIG. 5F, FIG. 5G, FIG. 5H, FIG. 5I, FIG. 5J, FIG. 6A, FIG. 6B,FIG. 6C and FIG. 7. In some embodiments, the user interface circuitry269 may be in communication with a display device (e.g., input-outputcircuitry 266, a display 116, a user device, or a display devicecommunicatively coupled thereto) and thus configured to transmit theuser interface data to the display device. For example, the userinterface circuitry 269 may be configured to generate user interfacedata and transmit the generated user interface data to the input-outputcircuitry 266, and the input-output circuitry 266 may be configured toreceive the user interface data and display the received user interfacedata on the display 116. In some embodiments, the user interfacecircuitry 269 may be configured to transmit the user interface data tothe communications circuitry 268, and the communications circuitry 268may be configured to transmit the user interface data to a user device.

In some embodiments, each of the user interface circuitry 269, impedancemonitor analysis circuitry 272, current monitor analysis circuitry 274,pulse monitor analysis circuitry 276, capacity monitor analysiscircuitry 278, HV monitor analysis circuitry 280, and crowbar triggercontrol signal generation circuitry 282 may include a separateprocessor, specially configured field programmable gate array (FPGA),application specific interface circuit (ASIC), or cloud utility toperform the above functions. In some embodiments, the hardwarecomponents described above with reference to user interface circuitry269, impedance monitor analysis circuitry 272, current monitor analysiscircuitry 274, pulse monitor analysis circuitry 276, capacity monitoranalysis circuitry 278, HV monitor analysis circuitry 280, and crowbartrigger control signal generation circuitry 282, may, for instance,utilize communications circuitry 268 or any suitable wired or wirelesscommunications path to communicate with a user device, each other, orany other suitable circuitry or device.

In some embodiments, one or more of the user interface circuitry 269,impedance monitor analysis circuitry 272, current monitor analysiscircuitry 274, pulse monitor analysis circuitry 276, capacity monitoranalysis circuitry 278, HV monitor analysis circuitry 280, and crowbartrigger control signal generation circuitry 282 may be hosted locally bythe apparatus 200. In some embodiments, one or more of the userinterface circuitry 269, impedance monitor analysis circuitry 272,current monitor analysis circuitry 274, pulse monitor analysis circuitry276, capacity monitor analysis circuitry 278, HV monitor analysiscircuitry 280, and crowbar trigger control signal generation circuitry282 (e.g., by one or more cloud servers) and thus need not physicallyreside on the apparatus 200. Thus, some or all of the functionalitydescribed herein may be provided by a remote circuitry. For example, theapparatus 200 may access one or more remote circuitries via any sort ofnetworked connection that facilitates transmission of data andelectronic information between the apparatus 200 and the remotecircuitries. In turn, the apparatus 200 may be in remote communicationwith one or more of the user interface circuitry 269, impedance monitoranalysis circuitry 272, current monitor analysis circuitry 274, pulsemonitor analysis circuitry 276, capacity monitor analysis circuitry 278,HV monitor analysis circuitry 280, and crowbar trigger control signalgeneration circuitry 282.

As described above and as will be appreciated based on this disclosure,embodiments of the present disclosure may be configured as systems,apparatuses, methods, mobile devices, backend network devices, computerprogram products, other suitable devices, and combinations thereof.Accordingly, embodiments may comprise various means including anycombination of software with hardware. Furthermore, embodiments may takethe form of a computer program product on at least one non-transitorycomputer-readable storage medium having computer-readable programinstructions (e.g., computer software) embodied in the storage medium.Any suitable computer-readable storage medium may be utilized includingnon-transitory hard disks, CD-ROMs, flash memory, optical storagedevices, or magnetic storage devices. As will be appreciated, anycomputer program instructions and/or other type of code described hereinmay be loaded onto a computer, processor or other programmableapparatus's circuitry to produce a machine, such that the computer,processor, or other programmable circuitry that executes the code on themachine creates the means for implementing various functions, includingthose described herein.

The user device may be embodied by one or more computing devices orsystems that also may include processing circuitry, memory, input-outputcircuitry, and communications circuitry. For example, a user device maybe a laptop computer on which an app (e.g., a GUI application) isrunning or otherwise being executed by processing circuitry. In yetanother example, a user device may be a smartphone on which an app(e.g., a webpage browsing app) is running or otherwise being executed byprocessing circuitry. As it relates to operations described in thepresent disclosure, the functioning of these devices may utilizecomponents similar to the similarly named components described abovewith respect to FIG. 2. Additional description of the mechanics of thesecomponents is omitted for the sake of brevity. These device elements,operating together, provide the respective computing systems with thefunctionality necessary to facilitate the communication of data with theEPT treatment instrument described herein.

Having described specific components of example devices involved in thepresent disclosure, example procedures for detecting fault conditionsare described below in connection with FIG. 3A, FIG. 3B, FIG. 3C, FIG.3D, FIG. 4A, FIG. 4B, FIG. 4C, FIG. 5A, FIG. 5B, FIG. 5C, FIG. 5D, FIG.5E, FIG. 5F, FIG. 5G, FIG. 5H, FIG. 5I, FIG. 5J, FIG. 6A, FIG. 6B, FIG.6C and FIG. 7.

FIG. 3A, FIG. 3B, FIG. 3C, FIG. 3D illustrate example block diagrams foran EPT treatment instrument in accordance with some example embodimentsdescribed herein. As shown in FIG. 3A, block diagram 300 comprisescomponents that illustrate, in some instances, an implementation of HVcircuitry 210, EPE circuitry 220, crowbar trigger circuitry 230, andmonitor circuitry 240. As shown in FIG. 3B, block diagram 320 comprisescomponents that illustrate, in some instances, an implementation ofprocessing circuitry 260, control circuitry 290, and ADC circuitry 296.As shown in FIG. 3C, block diagram 340 comprises components thatillustrate, in some instances, an implementation of additionalprocessing circuitry and input-output circuitry. As shown in FIG. 3D,block diagram 360 comprises components that illustrate, in someinstances, an implementation of additional power generation circuitryand input-output circuitry.

FIG. 4A, FIG. 4B, and FIG. 4C illustrate example circuitry blockdiagrams in accordance with some example embodiments described herein.As shown in FIG. 4A, circuitry block diagram 400 comprises HV relaycircuitry block 402 (e.g., showing signals received and transmitted byHV relay circuitry 222), monitor circuitry block 404 (e.g., showingsignals received and transmitted by monitor circuitry 240), processingcircuitry block 406 (e.g., showing signals received and transmitted byprocessing circuitry 260), and connector circuitry block 410 (e.g.,showing signals received and transmitted by HV circuitry 210, HV supplymonitor circuitry 252, and control circuitry 290, among others). Asfurther shown in FIG. 4A, processing circuitry block 406 may comprisemonitor analysis circuitry block 408 (e.g., showing signals received andtransmitted by monitor analysis circuitry 270).

As shown in FIG. 4B, circuitry block diagram 420 comprises a pluralityof signal monitoring blocks (e.g., showing signals received andtransmitted by ADC circuitry 296).

In some embodiments, each of the 0 ohm resistors shown in FIG. 4B may beplaced as close to a 30 position connector as possible.

As shown in FIG. 4C, circuitry block diagram 440 comprises a processingcircuitry block (e.g., showing signals received and transmitted byprocessing circuitry 260). In some embodiments, the component Y1 may beplaced as close to the processing circuitry block as possible. In someembodiments, processing circuitry 260 may be implemented, in part or inwhole, as the processing circuitry block shown in FIG. 4C.

FIG. 5A, FIG. 5B, FIG. 5C, FIG. 5D, FIG. 5E, FIG. 5F, FIG. 5G, FIG. 5H,FIG. 5I, and FIG. 5J illustrate example schematic diagrams in accordancewith some example embodiments described herein. As shown in FIG. 5A,circuitry 500 comprises gate drive circuitry and capacitor chargecircuitry. In some embodiments, gate drive circuitry 214 and capacitorcharge circuitry 216 may be implemented, in part or in whole, ascircuitry 500. In some embodiments, the AGND and PGND terminals ofcomponent U15 are configured to be connected by a single thick tracedirectly under component U15. In some embodiments, the component Q1 isdisposed to allow space for a heatsink, such as a clip on heatsink. Insome embodiments, the HV lines are configured to carry up to 90 amps ofcurrent.

As shown in FIG. 5B, circuitry 510 comprises crowbar trigger circuitry.In some embodiments, crowbar trigger circuitry 230 may be implemented,in part or in whole, as circuitry 510. In some embodiments, the crowbartrigger circuitry may use AND gates to receive signals frommicrocontrollers (e.g., processing circuitry 260) and analog components.In some embodiments, the high state of U21+U22 is normal operation; thelow state of U21+U22 transmits a crowbar activation signal.

In one illustrative example embodiment, the crowbar trigger circuitrycapacitor C49 is configured to be shorted by relay RE1, causing a 5Vsignal to be generated by transformer T1 across the capacitor chargecircuitry signals SCR_GATE and SCR_GATE_RTN electrically coupled tocircuitry 500 shown in FIG. 5A. This generated 5V signal is applied atthe gate of silicon controlled rectifier (SCR) U17 of circuitry 500shown in FIG. 5A, which brings component U17 into forward conductionmode, bypassing resistors R33, R34, R35, and R36. As a result, the +HVline is pulled to zero while all the charge on the HV capacitors C32,C33, and C34 flows through series resistors R17, R29, and R31.Additionally, when −HV_PULSE goes from 0 to −1300 Vdc, the inductor L10reverses polarity and mitigates the ensuing rush of current. Themajority of the current passes through high-wattage resistors R17, R29,and R31, which are also adjusted to alter the rate of decay of voltage.

In another illustrative example embodiment, circuitry 510 becomesenabled on power-up when the +5V_ISO rail charges capacitor C49. When anactive-low signal is induced on one of the 5 inputs (nMICRO_CROWBAR,nCAP_OV, nHV_OV, nOVER_CURRENT, and nPULSE_OV), the gate of component Q2becomes low turning on the PMOS. The capacitor C49 discharges throughcomponent Q2, sending a pulse through transformer T1 to the gate of SCRU17. Once the gate of the SCR receives a signal it becomes forwardbiased, allowing any energy stored in the HV capacitors C32, C33, andC34 to discharge. This energy is dissipated through resistors R17, R29,and R31 with inducer L10 limiting current spikes. On the event that theHV capacitors C32, C33, and C34 are charged and the system experiences apower failure, relay RE13 (e.g., relay RE13 is substantially similar torelay RES coupled to EPE Needle 1 shown in FIG. 5J, but is coupled toEPE Needle 6 rather than EPE Needle 1) will close allowing capacitor C49to discharge and activating the circuitry 510 as disclosed above.

In some embodiments, by including hardware-based crowbar trigger inputs(e.g., nCAP_OV, nHV_OV, nOVER_CURRENT, nPULSE_OV) in addition to asoftware-based crowbar trigger input (e.g., nMICRO_CROWBAR), thecircuitry 510 may react more quickly to any monitored conditions (e.g.,voltage, capacitance, current, pulse) which go out-of-specification thantypical processor-based EPT treatment systems due to the inherentlatencies in processor-based signal changes. In some embodiments, thecircuitry 510 is configured to initiate the termination of the deliveryof a therapeutic voltage pulse in less than 10 microseconds, followingthe identification of a fault condition. Accordingly, circuitry 510 isable to truncate not only a therapy sequence, but also an individualtherapy pulse, thereby increasing the inherent patient safety of the EPTtreatment instrument.

As shown in FIG. 5C, circuitry 520 comprises HV monitor circuitry. Insome embodiments, HV monitor circuitry 250 may be implemented, in partor in whole, as circuitry 520. In some embodiments, circuitry 520 isconfigured to receive an input+HV between 0 volts and 1,500 volts, andgenerate an output HV_MON between 0 volts and 4.983 volts. In someembodiments, HV_OV is set to 1,500 volts, and 5 volts VCC sets thetrigger to 1,512 volts. In some embodiments,HV_MON=(3.4K/(3.4K+1.025M))*HV+4.983V=0.003306 Ohms*1500V.

As shown in FIG. 5D, circuitry 530 comprises capacity monitor circuitry.In some embodiments, capacity monitor circuitry 248 may be implemented,in part or in whole, as circuitry 530. In some embodiments, circuitry530 is configured to receive an input CAP_V between 0 volts and 500volts, where +HV is between 0 volts and 1,500 volts. In someembodiments, CAP_V=0.33*HV+. In some embodiments,CAP_MON=(10K/(10K+990K))*CAP_V; 5V=0.01 Ohms*CAP_V; and 5V=0.00333*HV+.

As shown in FIG. 5E, circuitry 540 comprises pulse monitor circuitry. Insome embodiments, pulse monitor circuitry 246 may be implemented, inpart or in whole, as circuitry 540. In some embodiments, circuitry 540is configured to receive an input −HV_Pulse between 0 volts and −1,500volts, and generate an output PULSE_MON between 0 volts and 4.983 volts.In some embodiments, PULSE_MON=(3.4K/(3.4K+1.025M))*HV_PULSE; and(Inverted) 4.983V=0.003306 Ohms*(−1500V).

As shown in FIG. 5F, circuitry 550 comprises current monitor circuitryand impedance monitor circuitry. In some embodiments, current monitorcircuitry 244 and impedance monitor circuitry 242 may be implemented, inpart or in whole, as circuitry 550. In some embodiments, the measuredtissue resistance that will result in the detection of a fault conditionis between 0 Ohms and 20 Ohms. In some embodiments, IMPEDANCE_MON isbetween 4.1667 volts and 4.1528 volts. In some embodiments, an ADCelectrically coupled to circuitry 550, such as ADC2 shown in FIG. 3B, isconfigured to detect 11 steps between the difference of 0.0138V. In someembodiments, OPEN=0V; and 10K Skin Resistance=1.5625V.

In some embodiments, the K1 and K2 relays shown in FIG. 5F may beconfigured to switch between test pulses and therapy pulses/impedancemonitoring and ground to separate low voltage and high voltage circuitmodes. For example, when the K1 and K2 relays are switched to node 12,the circuitry 550 is in therapy pulse mode. In another example, when theK1 and K2 relays are switched to 10, the circuitry 550 is in impedancetesting mode. In some embodiments, the LV impedance check is terminatedwhen a fault is detected by executing a single software function. Insome embodiments, a single software function is executed whenever anyfault condition is detected, including a fault detected during an LVimpedance check. That single software function performs the followingactions, in the order listed: (1) prevent (or truncate) a therapy pulsefrom being delivered by de-asserting ENABLE PULSE; (2) disable the HVpower supply by de-asserting EN_HIGH_VOLTAGE; (3) activate the crowbartrigger by de-asserting nMICRO_CROWBAR; (4) open all “needle output”relays (RE1 to RE12) by de-asserting EN_HV_1 to EN_HV_6 and EN_RTN_1 toEN_RTN_6; (5) turn off the ARM button LED by de-asserting ARM LED ISO;(6) wait for the high voltage circuit to be drained to a voltage of lessthan 200 Vdc by polling HV_MON; (7) reset the software-controlledcrowbar trigger input by asserting nMICRO_CROWBAR; (8) set theidentified fault active; and (9) transition to the software “Fault”state.

As shown in FIG. 5G, circuitry 560 comprises digital potentiometer (pot)circuitry. In some embodiments, digital pot circuitry 292 may beimplemented, in part or in whole, as circuitry 560. In some embodiments,circuitry 560 may be configured to provide the voltage limit via avoltage divider-programmed voltage output which is compared to the pulseand capacitor voltages via op-amps U11A and U11B, allowing the crowbartrigger circuitry (e.g., circuitry 510) to activate in the case that thevoltage limit has been exceeded. The outputs of the voltage dividers areVAR_PULSE_V and VAR_CAP_V, which are programmed to represent the pulseand capacitance overvoltage limits, respectively, that activate thecrowbar trigger circuitry. The outputs are compared to the monitoredsignals PULSE_MON and CAP_MON, respectively. If the non-inverting inputis greater than the inverting input (PULSE_MON), then the output nPULSEis +Vcc. nPULSE is now high and crowbar trigger circuitry is activated.Feedback is disabled by D5. PULSE_MON must drive above VAR_PULSE_V inorder to switch the output to −Vcc. If the non-inverting input is lessthan PULSE_MON, then the output nPULSE is −Vcc, or ISO_GND. With theresistor R68 now in parallel with Rwb (the lower leg of the voltagedivider), the non-inverting input reduces from VAR_PULSE_V to a lowerthreshold voltage VL. Now PULSE_MON must drive below VL to cause theoutput to switch back to +Vcc. The effect of the diode is to addhysteresis when transitioning from the fault state to the normal stateto account for transient signal spikes, and to remove hysteresis duringnormal operation for safety reasons. In some embodiments, the ADDR1 andADDR0 pins of component U23 are connected to GND, which sets the I2Caddress to 0101111. In some embodiments, Rwb=(D/256)*Rab+55;1108=(D/256)*10000+55; D=27; HEX Number for the program=0x001B. In oneillustrative example embodiment, for a 400V applicator, the trip voltageis 1.33V (see capacity monitor, circuitry 530); VAR_CAP_V=1.33V;1.33V=(12*Rwb)/(10,000 KOhm); Rwb=1108 Ohms; and Raw=10,000-1108=8892Ohms.

As shown in FIG. 5H, circuitry 570 comprises digital pot HV controlcircuitry. In some embodiments, digital pot HV control circuitry 294 maybe implemented, in part or in whole, as circuitry 570. In someembodiments, the ADDR1 and ADDR0 pins of component U37 are connected to+3V3, which sets the I2C address to 0100000. In some embodiments,Rwb=(D/256)*Rab+55; 1108=(D/256)*10000+55; D=27; HEX Number for theprogram=0x001B. In one illustrative example embodiment, for a 400Vapplicator, the trip voltage is 1.33V (see capacity monitor, circuitry530); VAR_CAP_V=1.33V; 1.33V=(12*Rwb)/(10,000 KOhm); Rwb=1108 Ohms; andRaw=10,000-1108=8892 Ohms.

As shown in FIG. 5I, circuitry 580 comprises HV supply monitorcircuitry. In some embodiments, HV supply monitor circuitry 252 may beimplemented, in part or in whole, as circuitry 580.

As shown in FIG. 5J, circuitry 590 comprises HV relay circuitry. In someembodiments, HV relay circuitry 222 may be implemented, in part or inwhole, as circuitry 590. For example, where EPE circuitry 220 includessix EPE needle electrodes, HV relay circuitry 222 may include acircuitry 590 for each of the six EPE needle electrodes.

FIG. 6A, FIG. 6B, and FIG. 6C illustrate example pulse voltage signalsin accordance with some example embodiments described herein. As shownin FIG. 6A, user interface display screen 600 shows an example pulsevoltage signal 602 comprising a rising edge 604 and a falling edge 606of a pulse in a set of pulses. In some embodiments, the pulse monitoranalysis circuitry 276 may determine that: the width (e.g., duration) ofthe pulse in the set of pulses is 102.99 microseconds; the rise time ofthe rising edge 604 of the pulse in the set of pulses is 698nanoseconds; the fall time of the falling edge 626 of the pulse in theset of pulses is 1.901 microseconds.

As shown in FIG. 6B, user interface display screen 610 shows an examplepulse voltage signal 612 comprising a rising edge 614 of a pulse in aset of pulses. In some embodiments, the pulse monitor analysis circuitry276 may determine that the rise time of the rising edge 614 of the pulsein the set of pulses is 762 nanoseconds.

As shown in FIG. 6B, user interface display screen 620 shows an examplepulse voltage signal 622 comprising a falling edge 626 of a pulse in aset of pulses. In some embodiments, the pulse monitor analysis circuitry276 may determine that the fall time of the falling edge 626 of thepulse in the set of pulses is 1.894 microseconds.

Having described specific components of example devices involved in thepresent disclosure, example procedures for providing an EPT treatmentinstrument configured to detect fault conditions are described below inconnection with FIG. 7.

FIG. 7 illustrates an example flowchart 700 that contains exampleoperations for detecting fault conditions while electroporating cells ina tissue using a set of voltage pulses generated based on a voltagesupply according to some example embodiments described herein. Theoperations described in connection with FIG. 7 may, for example, beperformed by one or more components described with reference to EPTtreatment instrument 100 shown in FIG. 1; by apparatus 200 shown in FIG.2; by any other component described herein; or by any combinationthereof.

As shown by block 702, the apparatus 200 includes means, such as monitorcircuitry 240 or the like, for continuously monitoring a set ofcharacteristics of the voltage supply and the set of voltage pulses. Insome embodiments, the set of characteristics may comprise HV voltage,capacitor voltage, pulse voltage, current, impedance voltage, HV supplyvoltage, HV supply current, any other suitable characteristics, or anycombination thereof.

As shown by block 704, the apparatus 200 includes means, such as themonitor circuitry 240 or the like, for generating a first set of monitorsignals based on the set of characteristics. In some embodiments, thefirst set of monitor signals may include a set of analog monitorsignals, such as an analog continuously monitored HV voltage signal, ananalog continuously monitored capacitor voltage signal, an analogcontinuously monitored pulse voltage signal, an analog continuouslymonitored current signal, an analog continuously monitored impedancevoltage signal, an analog continuously monitored HV supply voltagesignal, an analog continuously monitored HV supply current signal, anyother suitable analog monitor signal, or any combination thereof. Insome embodiments, the monitor circuitry may be configured to transmitthe first set of monitor signals to any other circuitry describedherein, such as to ADC circuitry (e.g., ADC circuitry 296). The ADCcircuitry may provide for improved signal monitoring via faster samplingADCs (e.g., 2,000,000 samples per second).

As shown by block 706, the apparatus 200 includes means, such as themonitor circuitry 240 or the like, for detecting a first fault conditionbased on the first set of monitor signals. The first fault condition maycomprise an analog fault condition, such as an analog HV overvoltagecondition, an analog capacitor overvoltage condition, an analog pulseovervoltage signal condition, an analog overcurrent signal condition,any other suitable analog fault condition, or any combination thereof.

As shown by block 708, the apparatus 200 includes means, such as themonitor circuitry 240 or the like, for generating a first crowbartrigger activation signal. In some embodiments, the monitor circuitry240 may be configured to generate the first crowbar trigger activationsignal in response to detecting the first fault condition. In someembodiments, the first crowbar trigger activation signal may comprise ananalog crowbar trigger activation signal, such as an HV overvoltagesignal (nHV_OV), a capacitor overvoltage signal (nCAP_OV), a pulseovervoltage signal (nPULSE_OV), an overcurrent signal (nOVER_CURRENT),any other suitable analog crowbar trigger activation signal, or anycombination thereof. In some embodiments, the monitor circuitry 240 maybe configured to transmit the first crowbar trigger activation signal tocrowbar trigger circuitry (e.g., crowbar trigger circuitry 230).

As shown by block 710, the apparatus 200 includes means, such as monitoranalysis circuitry 270 or the like, for receiving a second set ofmonitor signals generated based on the first set of monitor signals. Thesecond set of monitor signals may include a set of digital monitorsignals, such as a digital continuously monitored HV voltage signal, adigital continuously monitored capacitor voltage signal, a digitalcontinuously monitored pulse voltage signal, a digital continuouslymonitored current signal, a digital continuously monitored impedancevoltage signal, a digital continuously monitored HV supply voltagesignal, a digital continuously monitored HV supply current signal, anyother suitable digital monitor signal, or any combination thereof. Insome embodiments, the monitor analysis circuitry 270 may be configuredto receive the second set of monitor signals from to any other circuitrydescribed herein, such as from ADC circuitry (e.g., ADC circuitry 296).For example, the first set of monitor signals may be a set of analogmonitor signals transmitted by the monitor circuitry 240 to the ADCcircuitry 296, and the second set of monitor signals may be a set ofdigital monitor signals generated by the ADC circuitry 296 based on theset of analog monitor signals and transmitted by the ADC circuitry 296to the monitor analysis circuitry 270.

As shown by block 712, the apparatus 200 includes means, such as themonitor analysis circuitry 270 or the like, for detecting a second faultcondition based on the second set of monitor signals. The second faultcondition may comprise a digital fault condition, such as a digital HVovervoltage condition, a digital capacitor overvoltage condition, adigital pulse overvoltage signal condition, a digital overcurrent signalcondition, any other suitable digital fault condition, or anycombination thereof.

As shown by block 714, the apparatus 200 includes means, such as themonitor analysis circuitry 270 or the like, for generating a secondcrowbar trigger activation signal. In some embodiments, the monitoranalysis circuitry 270 may be configured to generate the second crowbartrigger activation signal in response to detecting the second faultcondition. In some embodiments, the second crowbar trigger activationsignal may comprise a digital crowbar trigger activation signal(nMICRO_CROWBAR). In some embodiments, the monitor circuitry 240 may beconfigured to transmit the second crowbar trigger activation signal tocrowbar trigger circuitry (e.g., crowbar trigger circuitry 230).

As shown by block 716, the apparatus 200 includes means, such as themonitor analysis circuitry 270 or the like, for: receiving either thefirst crowbar trigger activation signal or the second crowbar triggeractivation signal; and, in response to either receiving the firstcrowbar trigger activation signal or receiving the second crowbartrigger activation signal, electrically disconnecting the capacitorcharge circuitry from the electroporation electrode circuitry.

In some embodiments, operations 702, 704, 706, 708, 710, 712, 714, and716 may not necessarily occur in the order depicted in FIG. 7. In someembodiments, one or more of the operations depicted in FIG. 7 may occursubstantially simultaneously. In some embodiments, one or moreadditional operations may be involved before, after, or between any ofthe operations shown in FIG. 7.

As described above and with reference to FIG. 1, FIG. 2, FIG. 3A, FIG.3B, FIG. 3C, FIG. 3D, FIG. 4A, FIG. 4B, FIG. 4C, FIG. 5A, FIG. 5B, FIG.5C, FIG. 5D, FIG. 5E, FIG. 5F, FIG. 5G, FIG. 5H, FIG. 5I, FIG. 5J, FIG.6A, FIG. 6B, FIG. 6C and FIG. 7, example embodiments of the presentdisclosure thus provide an EPT treatment instrument that provides for:electroporating cells in a tissue using a set of voltage pulsesgenerated based on a voltage supply; continuously monitoring a set ofcharacteristics of the voltage supply and the set of voltage pulses;generating a set of analog monitor signals based on the set ofcharacteristics; detecting a first fault condition (e.g., overvoltage,overcurrent) based on the analog set of monitor signals; detecting asecond fault condition (e.g., overvoltage, overcurrent) based on a setof digital monitor signals; and in response to either the detection ofthe first fault condition or the second fault condition, electricallydisconnecting, by crowbar trigger circuitry, the voltage pulses and thevoltage supply from the electroporation electrode needles to prevent theovervoltages and overcurrents from being applied to the patient.Accordingly, the example embodiments of the present disclosure provide:improved detection of a fault condition (e.g., overvoltage, overcurrent)by multiple, redundant analog and digital circuitries; and improvedprevention, by crowbar trigger circuitry, of any overvoltages orovercurrents from being applied to a patient.

FIG. 7 thus illustrates an example flowchart describing operationsperformed in accordance with example embodiments of the presentdisclosure. It will be understood that each block of the flowchart, andcombinations of blocks in the flowchart, may be implemented by variousmeans, such as devices comprising hardware, firmware, one or moreprocessors, and/or circuitry associated with execution of softwarecomprising one or more computer program instructions. For example, oneor more of the procedures described above may be performed by executionof program code instructions. In this regard, the program codeinstructions that, when executed, cause performance of the proceduresdescribed above may be stored by a non-transitory computer-readablestorage medium (e.g., memory 264) of a computing apparatus (e.g.,apparatus 200) and executed by a processor (e.g., processor 262) of thecomputing apparatus. In this regard, the computer program instructionswhich embody the procedures described above may be stored by a memory ofan apparatus employing an embodiment of the present disclosure andexecuted by a processor of the apparatus. As will be appreciated, anysuch computer program instructions may be loaded onto a computer orother programmable apparatus (e.g., hardware) to produce a machine, suchthat the resulting computer or other programmable apparatus provides forimplementation of the functions specified in the flowchart 700. Whenexecuted, the instructions stored in the computer-readable storagememory produce an article of manufacture configured to implement thevarious functions specified in the flowchart 700. The program codeinstructions may also be loaded onto a computer or other programmableapparatus to cause a series of operations to be performed on thecomputer or other programmable apparatus to produce acomputer-implemented process such that the instructions executed on thecomputer or other programmable apparatus provide operations forimplementing the functions specified in the operations of flowchart 700.Moreover, execution of a computer or other processing circuitry toperform various functions converts the computer or other processingcircuitry into a particular machine configured to perform an exampleembodiment of the present disclosure.

The flowchart operations described with reference to FIG. 7 supportcombinations of means for performing the specified functions andcombinations of operations for performing the specified functions. Itwill be understood that one or more operations of the flowchart, andcombinations of operations in the flowchart, may be implemented byspecial purpose hardware-based computer systems which perform thespecified functions, or combinations of special purpose hardware andcomputer instructions.

In some example embodiments, certain ones of the operations herein maybe modified or further amplified as described below. Moreover, in someembodiments additional optional operations may also be included. Itshould be appreciated that each of the modifications, optional additionsor amplifications described herein may be included with the operationsherein either alone or in combination with any others among the featuresdescribed herein.

The foregoing method descriptions and the process flow diagrams areprovided merely as illustrative examples and are not intended to requireor imply that the steps of the various embodiments must be performed inthe order presented. As will be appreciated by one of skill in the artthe order of steps in the foregoing embodiments may be performed in anyorder. Words such as “thereafter,” “then,” “next,” and similar words arenot intended to limit the order of the steps; these words are simplyused to guide the reader through the description of the methods.Further, any reference to claim elements in the singular, for example,using the articles “a,” “an” or “the,” is not to be construed aslimiting the element to the singular and may, in some instances, beconstrued in the plural.

While various embodiments in accordance with the principles disclosedherein have been shown and described above, modifications thereof may bemade by one skilled in the art without departing from the teachings ofthe disclosure. The embodiments described herein are representative onlyand are not intended to be limiting. Many variations, combinations, andmodifications are possible and are within the scope of the disclosure.Alternative embodiments that result from combining, integrating, and/oromitting features of the embodiment(s) are also within the scope of thedisclosure. Accordingly, the scope of protection is not limited by thedescription set out above, but is defined by the claims which follow,that scope including all equivalents of the subject matter of theclaims. Each and every claim is incorporated as further disclosure intothe specification and the claims are embodiment(s) of the presentdisclosure. Furthermore, any advantages and features described above mayrelate to specific embodiments, but shall not limit the application ofsuch issued claims to processes and structures accomplishing any or allof the above advantages or having any or all of the above features.

In addition, the section headings used herein are provided forconsistency with the suggestions under 37 C.F.R. § 1.77 or to otherwiseprovide organizational cues. These headings shall not limit orcharacterize the disclosure set out in any claims that may issue fromthis disclosure. For instance, a description of a technology in the“Background” is not to be construed as an admission that certaintechnology is prior art to any disclosure in this disclosure. Neither isthe “Summary” to be considered as a limiting characterization of thedisclosure set forth in issued claims. Furthermore, any reference inthis disclosure to “disclosure” or “embodiment” in the singular shouldnot be used to argue that there is only a single point of novelty inthis disclosure. Multiple embodiments of the present disclosure may beset forth according to the limitations of the multiple claims issuingfrom this disclosure, and such claims accordingly define the disclosure,and their equivalents, that are protected thereby. In all instances, thescope of the claims shall be considered on their own merits in light ofthis disclosure, but should not be constrained by the headings set forthherein.

Also, techniques, systems, subsystems, and methods described andillustrated in the various embodiments as discrete or separate may becombined or integrated with other systems, modules, techniques, ormethods without departing from the scope of the present disclosure.Other devices or components shown or discussed as coupled to, or incommunication with, each other may be indirectly coupled through someintermediate device or component, whether electrically, mechanically, orotherwise. Other examples of changes, substitutions, and alterations areascertainable by one skilled in the art and could be made withoutdeparting from the scope disclosed herein.

Many modifications and other embodiments of the disclosure set forthherein will come to mind to one skilled in the art to which theseembodiments pertain having the benefit of teachings presented in theforegoing descriptions and the associated figures. Although the figuresonly show certain components of the apparatus and systems describedherein, it is understood that various other components may be used inconjunction with the components and structures disclosed herein.Therefore, it is to be understood that the disclosure is not to belimited to the specific embodiments disclosed and that modifications andother embodiments are intended to be included within the scope of theappended claims. For example, the various elements or components may becombined, rearranged, or integrated in another system or certainfeatures may be omitted or not implemented. Moreover, the steps in anymethod described above may not necessarily occur in the order depictedin the accompanying drawings, and in some cases one or more of the stepsdepicted may occur substantially simultaneously, or additional steps maybe involved. Although specific terms are employed herein, they are usedin a generic and descriptive sense only and not for purposes oflimitation.

The invention claimed is:
 1. A system for electroporating cells in atissue using a set of voltage pulses generated based on a voltagesupply, the system comprising: a voltage generation circuitry inelectrical communication with a capacitor charge circuitry and a monitorcircuitry, wherein the voltage generation circuitry is configured togenerate the voltage supply, and transmit the voltage supply to thecapacitor charge circuitry; and the capacitor charge circuitry, whereinthe capacitor charge circuitry is in electrical communication with thevoltage generation circuitry, a crowbar trigger circuitry, the monitorcircuitry, and an electroporation electrode circuitry, and wherein thecapacitor charge circuitry is configured to receive the voltage supplyfrom the voltage generation circuitry, generate the set of voltagepulses based on the voltage supply, and transmit the set of voltagepulses to the electroporation electrode circuitry, the monitorcircuitry, wherein the monitor circuitry is in electrical communicationwith the voltage generation circuitry, the capacitor charge circuitry, amonitor analysis circuitry, and the crowbar trigger circuitry, andwherein the monitor circuitry is configured to continuously monitor aset of characteristics of the voltage supply and the set of voltagepulses, generate a first set of monitor signals based on the set ofcharacteristics, transmit the first set of monitor signals, detect afirst fault condition based on the first set of monitor signals, inresponse to detection of the first fault condition, generate a firstcrowbar trigger activation signal, and transmit the first crowbartrigger activation signal to the crowbar trigger circuitry; the monitoranalysis circuitry, wherein the monitor analysis circuitry is inelectrical communication with the crowbar trigger circuitry, and whereinthe monitor analysis circuitry is configured to receive a second set ofmonitor signals generated based on the first set of monitor signals,detect a second fault condition based on the second set of monitorsignals, in response to detection of the second fault condition,generate a second crowbar trigger activation signal, and transmit thesecond crowbar trigger activation signal to the crowbar triggercircuitry; the crowbar trigger circuitry, wherein the crowbar triggercircuitry is in electrical communication with the monitor circuitry andthe monitor analysis circuitry, and wherein the crowbar triggercircuitry is configured to receive the first crowbar trigger activationsignal from the monitor circuitry, receive the second crowbar triggeractivation signal from the monitor analysis circuitry, and in responseto either receipt of the first crowbar trigger activation signal orreceipt of the second crowbar trigger activation signal, electricallydisconnect the capacitor charge circuitry from the electroporationelectrode circuitry.
 2. The system of claim 1, wherein the first set ofmonitor signals is a set of analog monitor signals, wherein the secondset of monitor signals is a set of digital monitor signals.
 3. Thesystem of claim 1, wherein the voltage supply is a high voltage (HV)supply, and wherein a voltage of the HV supply is between about 1,000volts and 1,750 volts, and wherein an amperage of the HV supply isbetween about 40 amps and 60 amps.
 4. The system of claim 3, wherein thevoltage of the HV supply is about 1,500 volts, and wherein the amperageof the HV supply is about 50 amps.
 5. The system of claim 1, wherein aduration of each voltage pulse in the set of voltage pulses is betweenabout 50 microseconds and about 150 microseconds.
 6. The system of claim1, wherein the crowbar trigger circuitry is configured to electricallydisconnect the capacitor charge circuitry from the electroporationelectrode circuitry within about 10 microseconds of the detection of thefirst fault condition or the detection of the second fault condition. 7.The system of claim 1, wherein the voltage supply is a high voltage (HV)supply, and wherein the monitor circuitry comprises an HV monitorcircuitry configured to: continuously monitor an HV voltage of the HVsupply, wherein the set of characteristics comprises the continuouslymonitored HV voltage; generate a first continuously monitored HV voltagesignal based on the continuously monitored HV voltage, wherein the firstset of monitor signals comprises the first continuously monitored HVvoltage signal; detect a first HV overvoltage condition based on thefirst continuously monitored HV voltage signal, wherein the first faultcondition is the first HV overvoltage condition; and in response todetection of the first HV overvoltage condition, generate a first HVovervoltage signal, wherein the first crowbar trigger activation signalis the first HV overvoltage signal.
 8. The system of claim 7, whereinthe monitor analysis circuitry comprises an HV monitor analysiscircuitry and a crowbar trigger control signal generation circuitry,wherein the HV monitor analysis circuitry is configured to receive asecond continuously monitored HV voltage signal generated based on thefirst continuously monitored HV voltage signal, wherein the second setof monitor signals comprises the second continuously monitored HVvoltage signal, detect a second HV overvoltage condition based on thesecond continuously monitored HV voltage signal, wherein the secondfault condition is the second HV overvoltage condition, in response todetection of the second HV overvoltage condition, generate a second HVovervoltage signal, and transmit the second HV overvoltage signal to thecrowbar trigger control signal generation circuitry; and wherein thecrowbar trigger control signal generation circuitry is configured toreceive the second HV overvoltage signal from the HV monitor analysiscircuitry, in response to receipt of the second HV overvoltage signal,generate the second crowbar trigger activation signal, and transmit thesecond crowbar trigger activation control signal to the crowbar triggercircuitry.
 9. The system of claim 1, wherein the monitor circuitrycomprises capacity monitor circuitry configured to: continuously monitora capacitor voltage of the capacitor charge circuitry, wherein the setof characteristics comprises the continuously monitored capacitorvoltage; generate a first continuously monitored capacitor voltagesignal based on the continuously monitored capacitor voltage, whereinthe first set of monitor signals comprises the first continuouslymonitored capacitor voltage signal; detect a first capacitor overvoltagecondition based on the first continuously monitored capacitor voltagesignal, wherein the first fault condition is the first capacitorovervoltage condition; and in response to detection of the firstcapacitor overvoltage condition, generate a first capacitor overvoltagesignal, wherein the first crowbar trigger activation signal is the firstcapacitor overvoltage signal.
 10. The system of claim 9, wherein themonitor analysis circuitry comprises a capacity monitor analysiscircuitry and a crowbar trigger control signal generation circuitry,wherein the capacity monitor analysis circuitry is configured to receivea second continuously monitored capacitor voltage signal generated basedon the first continuously monitored capacitor voltage signal, whereinthe second set of monitor signals comprises the second continuouslymonitored capacitor voltage signal, detect a second capacitorovervoltage condition based on the second continuously monitoredcapacitor voltage signal, wherein the second fault condition is thesecond capacitor overvoltage condition, in response to detection of thesecond capacitor overvoltage condition, generate a second capacitorovervoltage signal, and transmit the second capacitor overvoltage signalto the crowbar trigger control signal generation circuitry; and whereinthe crowbar trigger control signal generation circuitry is configured toreceive the second capacitor overvoltage signal from the capacitymonitor analysis circuitry, in response to receipt of the secondcapacitor overvoltage signal, generate the second crowbar triggeractivation signal, and transmit the second crowbar trigger activationsignal to the crowbar trigger circuitry.
 11. The system of claim 1,wherein the monitor circuitry comprises a pulse monitor circuitryconfigured to: continuously monitor a pulse voltage of the set ofvoltage pulses, wherein the set of characteristics comprises thecontinuously monitored pulse voltage; generate a first continuouslymonitored pulse voltage signal based on the continuously monitored pulsevoltage, wherein the first set of monitor signals comprises the firstcontinuously monitored pulse voltage signal; detect a first pulseovervoltage condition based on the first continuously monitored pulsevoltage signal, wherein the first fault condition is the first pulseovervoltage condition; and in response to detection of the first pulseovervoltage condition, generate a first pulse overvoltage signal,wherein the first crowbar trigger activation signal is the first pulseovervoltage signal.
 12. The system of claim 11, wherein the monitoranalysis circuitry comprises a pulse monitor analysis circuitry and acrowbar trigger control signal generation circuitry, wherein the pulsemonitor analysis circuitry is configured to receive a secondcontinuously monitored pulse voltage signal generated based on the firstcontinuously monitored pulse voltage signal, wherein the second set ofmonitor signals comprises the second continuously monitored pulsevoltage signal, detect a second pulse overvoltage condition based on thesecond continuously monitored pulse voltage signal, wherein the secondfault condition is the second pulse overvoltage condition, in responseto detection of the second pulse overvoltage condition, generate asecond pulse overvoltage signal, and transmit the second pulseovervoltage signal to the crowbar trigger control signal generationcircuitry; and wherein the crowbar trigger control signal generationcircuitry is configured to receive the second pulse overvoltage signalfrom the pulse monitor analysis circuitry, in response to receipt of thesecond pulse overvoltage signal, generate the second crowbar triggeractivation signal, and transmit the second crowbar trigger activationsignal to the crowbar trigger circuitry.
 13. The system of claim 12,wherein the pulse monitor analysis circuitry is further configured to:determine a rise time of a rising edge of a pulse in the set of voltagepulses; and detect the second pulse overvoltage condition based on therise time.
 14. The system of claim 1, wherein the monitor circuitrycomprises a current monitor circuitry configured to: continuouslymonitor a current of the set of voltage pulses, wherein the set ofcharacteristics comprises the continuously monitored current; generate afirst continuously monitored current signal based on the continuouslymonitored current, wherein the first set of monitor signals comprisesthe first continuously monitored current signal; detect a firstovercurrent condition based on the first continuously monitored currentsignal, wherein the first fault condition is the first overcurrentcondition; and in response to detection of the first overcurrentcondition, generate a first overcurrent signal, wherein the firstcrowbar trigger activation signal is the first overcurrent signal. 15.The system of claim 14, wherein the monitor analysis circuitry comprisesa current monitor analysis circuitry and a crowbar trigger controlsignal generation circuitry, wherein the current monitor analysiscircuitry is configured to receive a second continuously monitoredcurrent signal generated based on the first continuously monitoredcurrent signal, wherein the second set of monitor signals comprises thesecond continuously monitored current signal, detect a secondovercurrent condition based on the second continuously monitored currentsignal, wherein the second fault condition is the second overcurrentcondition, in response to detection of the second overcurrent condition,generate a second overcurrent signal, and transmit the secondovercurrent signal to the crowbar trigger control signal generationcircuitry; and wherein the crowbar trigger control signal generationcircuitry is configured to receive the second overcurrent signal fromthe current monitor analysis circuitry, in response to receipt of thesecond overcurrent signal, generate the second crowbar triggeractivation signal, and transmit the second crowbar trigger activationsignal to the crowbar trigger circuitry.
 16. The system of claim 1,wherein: the monitor circuitry is in electrical communication with a setof relays; the monitor circuitry comprises an impedance monitorcircuitry configured to: generate a set of low voltage (LV) pulses,transmit the set of LV pulses to the electroporation electrodecircuitry, receive a set of LV return pulses from the electroporationelectrode circuitry, monitor a resistance of the tissue based on the setof LV return pulses, generate a first monitored impedance voltage signalbased on the monitored resistance, detect a first impedance testingfault condition based on the first monitored impedance voltage signal;and in response to detection of the first impedance testing faultcondition, generate a first set of relay deactivation signals, andtransmit the first set of relay deactivation signals to the set ofrelays; the electroporation electrode circuitry comprises the set ofrelays; and each relay in the set of relays is configured to receive oneof relay deactivation signals in the first set of relay deactivationsignals from the impedance monitor circuitry, and in response to receiptof the one of the relay deactivation signals in the first set of relaydeactivation signals, electrically disconnect the capacitor chargecircuitry from the electroporation electrode circuitry.
 17. The systemof claim 16, wherein: the monitor analysis circuitry comprises animpedance monitor analysis circuitry; the impedance monitor analysiscircuitry is configured to receive a second monitored impedance voltagesignal generated based on the first monitored impedance voltage signal,detect a second impedance testing fault condition based on the secondmonitored impedance voltage signal, in response to detection of thesecond monitored impedance voltage signal, generate a second set ofrelay deactivation signals, and transmit the second set of relaydeactivation signals to the set of relays; and each relay in the set ofrelays is configured to receive one of the relay deactivation signals inthe second set of relay deactivation signals from the impedance monitoranalysis circuitry, and in response to receipt of the one of the relaydeactivation signals in the second set of relay deactivation signals,electrically disconnect the capacitor charge circuitry from theelectroporation electrode circuitry.
 18. The system of claim 1, wherein:the monitor analysis circuitry is in electrical communication with a setof relays; the monitor analysis circuitry is further configured to inresponse to the detection of the second fault condition, generate a setof relay deactivation signals, and transmit the set of relaydeactivation signals to the set of relays; the electroporation electrodecircuitry comprises the set of relays; and each relay in the set ofrelays is configured to receive one of relay deactivation signals in theset of relay deactivation signals from the monitor analysis circuitry,and in response to receipt of the one of the relay deactivation signals,electrically disconnect the capacitor charge circuitry from theelectroporation electrode circuitry.
 19. An apparatus forelectroporating cells in a tissue using a set of voltage pulsesgenerated based on a voltage supply, the apparatus comprising: a monitorcircuitry in electrical communication with a crowbar trigger circuitry,wherein the monitor circuitry is configured to continuously monitor aset of characteristics of the voltage supply and the set of voltagepulses, generate a first set of monitor signals based on the set ofcharacteristics, transmit the first set of monitor signals, detect afirst fault condition based on the first set of monitor signals, inresponse to detection of the first fault condition, generate a firstcrowbar trigger activation signal, and transmit the first crowbartrigger activation signal to the crowbar trigger circuitry; a monitoranalysis circuitry in electrical communication with the crowbar triggercircuitry, wherein the monitor analysis circuitry is configured toreceive a second set of monitor signals generated based on the first setof monitor signals, detect a second fault condition based on the secondset of monitor signals, in response to detection of the second faultcondition, generate a second crowbar trigger activation signal, andtransmit the second crowbar trigger activation signal to the crowbartrigger circuitry; the crowbar trigger circuitry, wherein the crowbartrigger circuitry is in electrical communication with the monitorcircuitry and the monitor analysis circuitry, and wherein the crowbartrigger circuitry is configured to receive the first crowbar triggeractivation signal from the monitor circuitry, receive the second crowbartrigger activation signal from the monitor analysis circuitry, and inresponse to either receipt of the first crowbar trigger activationsignal or receipt of the second crowbar trigger activation signal,electrically disconnect the voltage supply from an electroporationelectrode circuitry.
 20. A method for electroporating cells in a tissueusing a set of voltage pulses generated based on a voltage supply, themethod comprising: generating, by a voltage generation circuitry, thevoltage supply; transmitting, by the voltage generation circuitry, thevoltage supply to capacitor charge circuitry; receiving, by thecapacitor charge circuitry, the voltage supply from the voltagegeneration circuitry; generating, by the capacitor charge circuitry, theset of voltage pulses based on the voltage supply; transmitting, by thecapacitor charge circuitry, the set of voltage pulses to anelectroporation electrode circuitry; continuously monitoring, by amonitor circuitry, a set of characteristics of the voltage supply andthe set of voltage pulses; generating, by the monitor circuitry, a firstset of monitor signals based on the set of characteristics;transmitting, by the monitor circuitry, the first set of monitorsignals; detecting, by the monitor circuitry, a first fault conditionbased on the first set of monitor signals; in response to detecting thefirst fault condition, generating, by the monitor circuitry, a firstcrowbar trigger activation signal; transmitting, by the monitorcircuitry, the first crowbar trigger activation signal to crowbartrigger circuitry; receiving, by a monitor analysis circuitry, a secondset of monitor signals generated based on the first set of monitorsignals; detecting, by the monitor analysis circuitry, a second faultcondition based on the second set of monitor signals; in response todetecting the second fault condition, generating, by the monitoranalysis circuitry, a second crowbar trigger activation signal;transmitting, by the monitor analysis circuitry, the second crowbartrigger activation signal to the crowbar trigger circuitry; receiving,by the crowbar trigger circuitry, either the first crowbar triggeractivation signal or the second crowbar trigger activation signal; andin response to either receiving the first crowbar trigger activationsignal or receiving the second crowbar trigger activation signal,electrically disconnecting, by the crowbar trigger circuitry, thecapacitor charge circuitry from the electroporation electrode circuitry.